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Biomedical subjects

C Nielsen

Publications and source records attributed to C Nielsen.

At least 127 records · Page 7Linked to original sources
PubMed1992

Synergistic antiviral effect in vitro of azidothymidine and amphotericin B methyl ester in combination on HIV infection.

The nucleoside analogue azidothymidine (AZT) and the methyl ester of amphotericin B (AME) were assayed for antiviral effect on HIV infection singly and in combination. Both compounds were effective in inhibiting HIV infection of MT-4 cells. At concentrations where either compound alone had no significant effect on infection, the compounds in combination were potent inhibitors of HIV as evaluated by reduction in HIV antigen production and HIV induced cytopathic effect. These results indicate that a combination therapy employing compounds with different modes of action like AZT and AME may have synergistic antiviral properties. Amphotericin B itself significantly reduced HIV infectivity in vitro and should not be used as an antifungal agent in cultures intended to propagate HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Trend towards decreased survival in patients infected with HIV resistant to zidovudine.

The survival of 35 patients with AIDS or advanced HIV infection on treatment with zidovudine was related to the viral sensitivity to the drug and to the CD4+ cell count. 14 patients died, the survivors were followed up for an average of 804 days. In a univariate Cox model, survival was strongly related to log IC90 (p = 0.0003) and to the CD4+ count (p = 0.0002). In a bivariate model, log IC90 and the CD4+ count contributed to the prediction of survival (p = 0.12 and 0.06, respectively). Large studies of combination or alternation therapy with several anti-HIV drugs should be given high priority.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Synthesis of 5-homologous AZT and D4T derivatives.

The 3'-iodonucleosides 4 have been synthesized by condensation of silylated 5-alkyluracils 2 with methyl 5-O-tert-butyldiphenylsilyl-2,3-dideoxy-3-iodo-D-threo-pentofur anoside (3). 4 was treated with sodium azide and the deprotected nucleoside 5 was subsequently obtained by treatment with tetrabutylammonium fluoride. The nucleoside 4 produced the corresponding 2',3'-didehydro-2',3'-dideoxy nucleoside 6 and 3',4'-didehydro-2',3'-dideoxy nucleoside 7 in elimination reactions on treatment with sodium methoxide.

Antiviral Agents↗
PubMed1992

Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies.

The capacity of consecutive human sera to neutralize sequentially obtained autologous virus isolates was studied. HIV-1 was isolated three times over a 48-164-week period from three individuals immediately after seroconversion and from two individuals in later stages of infection. Development of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay. Titers of neutralizing antibodies against late virus isolates were generally low compared to initial neutralizing titers against primary virus isolates. The delay in appearance of neutralizing antibodies to the dominant viral strain at any time in the patient and the emergence of neutralization resistant escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection.

HIV Antibodies↗
PubMed1991

[Therapeutic monitoring of drug concentration in blood. Are the analyses correctly ordered?].

In order to use therapeutic drug monitoring, it is important that a therapeutic range is established, and that doctors are familiar with the conditions necessary for this. Information and timing of 175 drug requests (digoxin, lithium, theophylline, valproic acid and carbamazepine) from the out-patients of the Department of Clinical Chemistry were studied by means of a questionnaire. The relationship between the last dose and blood sampling time showed great variation between the various drugs. 37% of the patients had received no information from their doctor concerning the correct time of the last dose of the relevant drug before sampling. The results showed the importance of thorough information to the patients by their doctors about the time of the last dose prior to sampling.

Blood Chemical Analysis↗
PubMed1991

Isolation of HIV from cultures of purified CD4+ lymphocytes.

Isolation of HIV from cultures of CD4+ lymphocytes purified from peripheral blood by indirect panning was optimized and evaluated. Infectious HIV was isolated by single isolation attempts in 98% of 102 HIV-antibody-positive patients (55 had AIDS or ARC and 47 were clinically healthy). The average culture time required for positive cultures was largely independent of the CD4 count of the patients and 87% of the positive isolation cultures from both groups of patients became positive within 14 days of culture. An evaluation of the possible influence of media additives on propagation of HIV showed that: amphotericin-B had a suppressive effect on HIV replication at concentrations recommended for anti-fungal activity; recombinant and human interleukin-2 were equally suitable for both isolation cultures and for propagation of HIV, and polybrene, at a concentration of 2 micrograms/ml in the culture medium had a beneficial effect.

Amphotericin B↗
PubMed1991

Effect of anti-carbohydrate antibodies on HIV infection in a monocytic cell line (U937).

Monoclonal antibodies (mAbs) against carbohydrate epitopes of gp120 have recently been found to inhibit HIV infection of lymphocytes in vitro thereby opening new possibilities for vaccine considerations. Antibody-dependent enhancement of infection has however come increasingly into focus. This study therefore investigated the neutralization of HIV in a monocytic cell line (U937) using mAbs against these carbohydrate gp120-epitopes. While antibodies against one of the epitopes (AI) neutralized infection of U937 cells despite binding to the Fc-receptor, one mAb against the sialosyl-Tn epitope enhanced infection. This enhancement was independent of complement and could be blocked by mAb Leu3a against the CD4-receptor. The study indicated that enhancement of infection in monocytic cells can occur by the same anti-carbohydrate antibodies that neutralize infection in lymphocytes, and that antibody mediated enhancement may depend on location of the epitope on gp120 rather than whether the antibody binds Fc-receptors.

Antibodies, Monoclonal↗
PubMed1991

A model for cortical 40 Hz oscillations invokes inter-area interactions.

Computer simulation of the dynamics of neuronal assemblies within minicolumns, and of the interactions between minicolumns in different cortical areas, has produced a quantitative explanation of the 35-60 Hz oscillations recently observed in adult cat striate cortices. The observed behavior suggests an association mechanism that exploits the NMDA receptor's properties. Detectable oscillations are predicted in cortical areas not directly stimulated, provided these are associatively linked with areas receiving sensory input.

Animals↗
PubMed1991

Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors.

Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can be a target for MAb-mediated virus neutralization.

ABO Blood-Group System↗
PubMed1991

Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus.

The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells. This inhibition was found in infection of both lymphocytic cells and monocytoid cells. Viruses tested included six HIV-1 and five HIV-2 isolates propagated in different cells, as well as infectious plasma from AIDS patients. The antiviral effect of anti-Tn MAbs occurred by specific binding of the MAb to the virus; this binding was inhibitable by pure Tn antigen, and indications were found that this inhibition occurred at a pre-entry step. Boosting the naturally occurring low-titer anti-Tn activity may be of prophylactic value, as suggested by the in vitro neutralization found in this study.

Antibodies, Monoclonal↗
PubMed1991

Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody.

Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited in a concentration dependent manner by MAb against the beta-chain but not against the alpha-chain. No cross-reactivity was found between MAb against LFA-1 and against the CD4 receptor (MAb Leu3a). MAbs against the beta-chain and the CD4 receptor were found to act synergistically in inhibiting HIV infection. These data indicate that the beta-chain of LFA-1 in addition to the CD4 receptor may be involved in HIV infection in vitro.

Antibodies, Monoclonal↗
PubMed1991

Inhibition of human immunodeficiency virus 1 (HIV-1) and herpes simplex virus 1 (HSV-1) infectivity with a broad range of lectins.

Five lectins with specificity for N- and O-linked oligosaccharides were examined for inhibition of HIV-1 and HSV-1 infectivity in vitro. HIV-1 isolate HTLVIIIB was preincubated with lectin and subsequently inoculated onto MT-4 cells. Lectins specific for N-linked oligosaccharides blocked HIV infection in nanomolar-micromolar concentrations, but no anti-HIV effect was found with the lectin HPA, mainly reacting with O-linked oligosaccharides. HSV-1 infectivity was measured in a plaque reduction assay using Vero cells, and while both N- and O-linked oligosaccharide -specific lectins inhibited HSV-1 infection, the most potent inhibition was found with the lectin HPA. These results indicate that lectins may have a broad antiviral effect on enveloped viruses only limited by types of oligosaccharides present on individual viruses.

Animals↗
PubMed1991

Prevalence of HIV infection in seronegative high-risk individuals examined by virus isolation and PCR.

HIV seronegative individuals with high-risk behavior were tested for HIV infection by sensitive virus isolation techniques using T4 lymphocytes and monocyte/macrophages, and by detection of proviral DNA using PCR with three different sets of nested primers. No evidence of HIV infection was found among the 31 seronegative high-risk subjects, either by virus isolation of by PCR (97.5% confidence limits, 0-11). Our results indicate that ongoing HIV infection in seronegative persons at high risk of infection is a rare event.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Sarcomatous mesothelioma of the pleura with cerebral metastases.

A case of sarcomatous pleural mesothelioma in a 22-year-old woman is presented. There was no history of occupational exposure to asbestos. Twenty months after the first symptoms occurred the patient noticed weakness in the right arm. A computed tomography scan of the brain showed multiple metastases. The patient died 10 days later.

Adult↗
PubMed1990

Derivatives of amphotericin inhibit infection with human immunodeficiency virus in vitro by different modes of action.

Three water-soluble derivatives of amphotericin B were tested for inhibition of HIV infection in vitro. The compounds amphotericin B methyl ester (AME) and N-(N'-(2-(4'-methylmorpholinio)ethyl)N"-cyclohexyl guanyl) amphotericin B methyl ester (MCG) inhibited HIV infection by 50% at 1 microgram/ml; N-(N'-(3-dimethylaminopropyl)N"-ethyl guanyl) amphotericin B (DAPEG) did so at 5-11 micrograms/ml. While the virus-inhibitory effect of AME was due to an interaction with target lymphocytes, the effect of MCG was due to a direct anti-viral action. AME increased the potential of infected cells to fuse with uninfected cells, but MCG had no significant effect on cell fusion. All compounds had a lower cellular toxicity than amphotericin B and were not toxic at concentrations below 20 micrograms/ml.

Amphotericin B↗
PubMed1990

Prediction of outcome in late-stage cardiomyopathy.

One hundred thirty-three patients with dilated heart failure, 80 with coronary artery disease, and 53 with idiopathic dilated cardiomyopathy were followed for a mean of 29 months. Patients with ischemic heart disease had a worse prognosis than those classified as having idiopathic cardiomyopathy. Features from history, physical examination, and diagnostic tests done when patients were referred to our clinic were checked for univariate association with survival and were used in Cox model survival analysis to define risk groups. Neither the overall group nor either subgroup showed a relationship between ejection fraction and survival. The best variables for predicting long-term mortality included underlying coronary artery disease, basal systolic blood pressure of less than 120 mm Hg, presence of congestion on chest radiogram, and age over 64. Other variables did not improve risk prediction in the overall group. Among patients with ischemic heart disease, blood pressure, congestion, maximal heart rate on treadmill test, and the presence of left bundle branch block on the initial electrocardiogram all contributed. Only systolic blood pressure and the symptom score were related to survival in idiopathic cardiomyopathy.

Aged↗
PubMed1990

Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization.

Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N- and O-linked carbohydrate epitopes (LeY, A1, and sialyl-Tn) were able to block infection by cell-free virus as well as inhibit syncytium formation. Inhibition of virus infectivity was independent of virus strain (HTLVIIIB or patient isolate SSI-002), the cell line used for virus propagation (H9 or MT4), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define carbohydrate structures expressed by the viral envelope glycoprotein gp120, indicating that glycans of the viral envelope are possible targets for immunotherapy or vaccine development or both.

Antibodies, Monoclonal↗